International Meeting for Autism Research: Brain Region-Specific Nurotrophin Changes in Autism

Brain Region-Specific Nurotrophin Changes in Autism

Friday, May 21, 2010
Franklin Hall B Level 4 (Philadelphia Marriott Downtown)
1:00 PM
E. M. Sajdel-Sulkowska , Psychiatry, Harvard Medical School, Harvard Institute of Medicine, BWH, Boston, MA
Background: We have previously reported increased oxidative stress and neurotrophin-3 (NT-3) levels in autistic cerebella. Furthermore, an increase in oxidative stress markers 3-nitrotyrosine (3-NT) and NT-3 showed brain region-specific distribution.

Objectives: The focus of the current study was to determine the levels of brain-derived neurotrophic factor (BDNF) and compare its expression to NT-3 levels across regions of autistic and control brains.

Methods: The levels of NT-3 and BDNF were measured by ELISA in homogenates prepared from frozen individual brain regions of an autistic male donor (age 14.3 years; PMI 9 hours) and matched control male donor (age, 14.5 years; PMI, 16 hours) and in cerebellar homogenates of 5 control and 6 autistic cases matched for age and PMI.  

Results: Cerebellar NT-3 and BDNF levels were increased in autistic cerebella. NT-3 was increased by 40.3% from 561.8 pg/g in control to 788.1 pg/g in autism (p=0.034). Similarly, cerebellar BDNF levels were increased by 54.2% from 346.6 pg/g in controls to 534.5 pg/g in autism (p=0.047).  Both NT-3 and BDNF were increased in BA46. In contrast, both neurotrophins were decreased in BA11 and BA22. In the hippocampus, NT-3 levels were increased while the BDNF levels were decreased.

Conclusions: Our results provide evidence of both over- and under-expression of neurotrophic factors, NT-3 and BDNF, in selected brain regions in autism. The increase is most evident in brain areas associated with attention and working memory, motor coordination, and integration of sensory perception (BA46 and cerebellum). Under-expression of NT-3 and BDNF is evident in BA11 and BA22 (Werickes's area) - brain areas associated with speech processing, decision making, emotional and cognitive processing, learning and social behavior. These two areas also showed the greatest increase in levels of the oxidative stress marker 3-NT, a pattern consistent with clinical manifestations of autism. Since NT-3 and BDNF are critical for growth, differentiation, and survival of neurons, their region-specific deficiency could contribute to the focal nature of autistic pathology resulting in the autistic phenotype. Clearly, further characterization of oxidative stress and neurotrophin levels across brain regions is necessary to increase our understanding of autistic pathology and to devise means of its prevention and treatment.

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